Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis

Abstract

Background Tumor-Treating Fields (TTFields) is an emerging treatment modality for glioblastoma (GBM). Studies have shown a good safety profile alongside improved efficacy in newly diagnosed GBM (ndGBM), while a less clear effect was shown for recurrent GBM (rGBM). Despite regulatory support, sectors of the neuro-oncology community have been reluctant to accept it as part of the standard treatment protocol. To establish an objective understanding of TTFields' mechanism of action, safety, efficacy, and economical implications, we conducted a systematic literature review and meta-analysis. Methods A systematic search was conducted in PubMed, Scopus, and Cochrane databases. Twenty studies met the pre-defined inclusion criteria, incorporating 1,636 patients (542 ndGBM and 1,094 rGBM), and 11,558 patients (6,403 ndGBM and 5,155 rGBM) analyzed for the clinical outcomes and safety endpoints, respectively. Results This study demonstrated improved clinical efficacy and a good safety profile of TTFields. For ndGBM, pooled median OS and PFS were 21.7 (95%CI=19.6-23.8) and 7.2 (95%CI=6.1-8.2) months, respectively. For rGBM, pooled median OS and PFS were 10.3 (95%CI=8.3-12.8) and 5.7 (95%CI=2.8-10) months, respectively. Compliance of ≥75% was associated with an improved OS and the predominant adverse events were dermatologic, with a pooled prevalence of 38.4% (95%CI=32.3-44.9). Preclinical studies demonstrated TTFields' diverse molecular mechanism of action, its potential synergistic efficacy, and suggest possible benefits for certain populations. Conclusions This study supports the use of TTFields for GBM, alongside the standard-of-care treatment protocol and provides a practical summary, discussing the current clinical and pre-clinical aspects of the treatment and their implication on the disease course.

Updates in IDH-Wildtype Glioblastoma

“…The EF-14 trial was an open-label, non-sham-controlled randomized phase III trial investigating the addition of TTF to standard therapy and demonstrated an improvement in median OS (20.9 versus 16 months) and PFS (6.7 versus 4 months) without compromising the health-related quality of life (HRQoL) [ 79 – 81 ]. However, compliance with TTF might be a limiting factor for its implementation in real-world practice [ 82 ]. A sub-group analysis from the same trial [ 83 ] has shown that the minimum average compliance rate threshold is 50% for a clinical gain in PFS (HR 0.70, 95% CI 0.47–1.05) and OS (HR 0.67, 95% CI 0.45–0.99) to be attained with a stepwise increase in both outcomes with higher compliance rates.…”

Effectiveness of Flattening-Filter-Free versus Flattened Beams in V79 and Glioblastoma Patient-Derived Stem-like Cells

“…Tumor-Treating Fields (TTFields) are emerging radiation treatment modalities for GBM, which has shown a good safety profile and better efficacy in newly diagnosed GBM, while a less clear effect was shown for recurrent GBM [ 3 ].…”

“…FFF beams allow up to a four-fold increase in the dose rate, thus reducing the probability of the patient’s motion and increasing his comfort. At state of the art, FFF is a technique already experienced in clinical settings in Stereotactic Body Radiation Therapy (SBRT) of vertebral, lung, liver, or intracranial tumors [ 3 ] thanks to the generated high gradient dose distribution hence the benefit of limiting normal tissue damage while preserving the tumor control rate.…”

Stages of stereotactic radiosurgery in the treatment of recurrent glioblastomas

“…Рецидив пов'язаний з майже універсальною смертністю. Медіанна виживаність після рецидиву становить від 9 до 20 міс [6][7][8] залежно від стратегії лікування.…”